Tumor proliferation suppressed, immune function restored, and harmful DNA cleared with no adverse reactions reported
Glioblastoma multiforme (GBM) remains among the deadliest primary brain cancers, notoriously resistant to current treatments. A 2025 pilot clinical trial evaluated whether a short-course combination of oral resveratrol, a polyphenol commonly derived from grapes, and copper, a trace mineral, could biologically alter glioblastoma tumor tissue before surgical removal. This intervention targeted extracellular DNA and protein complexes known as cell-free chromatin particles (cfChPs). These fragments, released from dying tumor cells, can increase inflammation, suppress the immune system, and promote further tumor growth.
Clinical Trial Design and Patient Cohort
Twenty patients diagnosed with GBM awaiting surgical removal of their tumors were enrolled. Ten patients received a brief oral regimen of resveratrol (5.6 mg) and copper (560 ng), administered four times daily for approximately 11 days before surgery. The other ten patients served as a control group and received no intervention. Tumor samples obtained during surgery were analyzed using microscopy and genetic sequencing to evaluate biological changes.
Observed Tumor Biological Responses
Removal of Harmful DNA Fragments
cfChPs were abundant in untreated glioblastoma samples. These chromatin particles actively induce inflammation, damage surrounding healthy cells, and help tumors evade immune detection. In patients treated with resveratrol and copper, these damaging DNA fragments were dramatically reduced or completely removed, indicating that the treatment effectively cleared this harmful cellular debris.
Suppression of Tumor Growth Markers
Tumors from treated patients exhibited notable decreases in biological markers associated with cancer growth and stem-cell characteristics. For instance, Ki-67, a protein indicating rapid cell division and tumor growth, was significantly reduced. Stem-cell markers SOX2 and Oct4, which indicate the tumor’s ability to regenerate and resist treatment, were also markedly decreased. These reductions imply the intervention can weaken glioblastoma’s growth and recurrence potential.
Reduction of Immune Checkpoint Proteins
Tumors often produce specific proteins called immune checkpoints, such as PVRIG, PD-L1, and TIM-3. These proteins normally prevent healthy immune cells (such as T-cells) from attacking cancer cells, allowing tumors to grow unchecked. In treated patients, these immune-suppressing proteins were significantly reduced, suggesting the treatment helped restore the immune system’s ability to detect and potentially eliminate tumor cells.
Favorable Genetic Reprogramming
Detailed genetic analyses (transcriptome sequencing) of tumor tissue showed significant shifts toward increased activity of genes promoting cell death (apoptosis), and decreased activity of genes that help tumor cells survive and evade immune detection. Specifically, a gene called PVRIG-2P, associated with suppression of immune function, was strongly downregulated. This indicates a meaningful genetic reprogramming toward tumor vulnerability.
Clinical Relevance and Safety Outcomes
Minimal Toxicity and High Safety Profile
Remarkably, despite the clear biological effects observed, patients receiving resveratrol and copper reported no adverse reactions. Additionally, the copper dose used was exceptionally low (less than 1% of typical daily recommendations), highlighting the intervention’s safety and practicality. Its simplicity, safety, and low cost make this combination particularly appealing, especially in resource-limited healthcare settings.
Significance for Clinical Practice
This pilot trial represents the first successful human clinical application targeting cfChPs in glioblastoma tumors, underscoring a novel therapeutic avenue. The rapid removal of harmful DNA fragments from the tumor environment occurred within days, suggesting swift biological responsiveness. Tumors treated with resveratrol and copper displayed clear reductions in crucial tumor growth indicators, such as Ki-67, and key stem-cell markers like SOX2 and Oct4, directly linking the therapy to decreased tumor regenerative capacity and growth potential.
The treatment effectively lowered immune checkpoint proteins, vital to the tumor’s ability to evade immune detection, potentially restoring immune function and enabling T-cells to recognize and attack cancer cells. Genetic sequencing further confirmed shifts towards enhanced apoptosis and reduced tumor cell survival mechanisms. The suppression of the gene PVRIG-2P highlighted significant genomic reprogramming towards tumor vulnerability.
These remarkable biological changes were achieved without toxicity or adverse effects. The intervention’s ease of administration, low dose requirements, and cost-effectiveness highlight its potential in global clinical settings, particularly where resources are limited. These findings suggest that this treatment strategy could become an essential adjunctive therapy, significantly altering tumor biology without relying solely on conventional chemotherapy or radiation.
Source Reference
Bandiwadekar C, Devi NL, Moiyadi AV, et al. Downregulation of cancer hallmarks and immune checkpoints in patients with glioblastoma following a short course of the pro-oxidant combination of resveratrol and copper. *medRxiv*. Preprint posted April 22, 2025. doi:10.1101/2025.02.19.25322384
Further Reading
New Hope in Fight Against Aggressive, Often Hard to Treat Brain Tumor
Nano-medicine & Ancient Wisdom: Homeopathy in Cancer Care
Integrative Cancer Treatment: An Effective Approach Using Adjunctive High-Dose IVC
